Transgenic overexpression of BMP4 increases astroglial and decreases oligodendroglial lineage commitment

William A. Gomes, Mark F. Mehler, John A. Kessler

Research output: Contribution to journalArticle

204 Scopus citations

Abstract

Bone morphogenetic proteins (BMPs) promote astrocytic differentiation of cultured subventricular zone stem cells. To determine whether BMPs regulate the astrocytic lineage in vivo, transgenic mice were constructed that overexpress BMP4 under control of the neuron-specific enolase (NSE) promoter. Overexpression of BMP4 was first detectable by Western analysis on embryonic day 16 and persisted into the adult. The overexpression of BMP4 resulted in a remarkable 40% increase in the density of astrocytes in multiple brain regions accompanied by a decrease in the density of oligodendrocytes ranging between 11 and 26%, depending on the brain region and the developmental stage. No changes in neuron numbers or the pattern of myelination were detected, and there were no gross structural abnormalities. Similar phenotypes were observed in three independently derived transgenic lines. Coculture of transgenic neurons with neural progenitor cells significantly enhanced astrocytic lineage commitment by the progenitors; this effect was blocked by the BMP inhibitor Noggin, indicating that the stimulation of astrogliogenesis was due to BMP4 release by the transgenic neurons. These observations suggest that BMP4 directs progenitor cells in vivo to commit to the astrocytic rather than the oligodendroglial lineage. Further, differentiation of radial glial cells into astrocytes was accelerated, suggesting that radial glia were a source of at least some of the supernumerary astrocytes. Therefore, BMPs are likely important mediators of astrocyte development in vivo.

Original languageEnglish (US)
Pages (from-to)164-177
Number of pages14
JournalDevelopmental Biology
Volume255
Issue number1
DOIs
StatePublished - Mar 1 2003

Keywords

  • Astrocyte
  • BMP4
  • Brain development
  • Gliogenesis
  • Oligodendrocyte
  • Radial glia
  • Stem cell

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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